The present invention relates to adsorption membranes, including microporous polymer membranes with silicon dioxide particles modified with hydrocarbon ligands having 2 to 24 carbon atoms embedded in them as adsorbent particles. Furthermore, the present invention also relates to a method of producing the inventive adsorption membranes as well as devices which include the adsorption membranes.
In the past, a variety of analytical methods have been developed which necessitate removing various substances such as solvents, low molecular ions and impurities from solutions such as peptide solutions which contain macromolecules in order to obtain sufficiently concentrated and purified samples for the respective analysis. Because of the sensitivity of these analytical methods, even small quantities of the aforementioned secondary constituents present in a sample to be analyzed can have a very negative effect on the analytical results.
One possibility of performing the separation described above is by adsorption, where components of a fluid, which may be individual molecules, associates or particles, are bound to the surface of a solid that is brought in contact with the fluid. A solid that is capable of adsorption is called an adsorbent, while the component to be adsorbed is called the adsorbate. Adsorption can be used technically for “adsorptive separation of substances,” which is performed in equipment known as adsorbers. An adsorbent with a high percentage of coarse pores running through it is also known as a “perfusion matrix.”
The adsorbate is known as the “target substance” when the goal is to recover it from the fluid, but it is called a “contaminant” when it is to be removed from the fluid. In the first case, the adsorption must be reversible, and adsorption is followed as the second process step by “elution” of the adsorbate under altered conditions (composition and/or temperature of the fluid). A target substance may be present as the only component in the fluid, so that the substance separation consists of a simple increase in concentration, or there may be multiple components which are to be separated. In this case, at least one of the two process steps must be “selective,” i.e., must take place to a different extent for each of the components to be separated. If the fluid is a liquid, adsorptive separation of substances (not including gas chromatography) is also referred to as chromatography and the fluid is known as the medium. The mass of the adsorbate bound in equilibrium is known as “static capacity,” based on the unit of mass of the adsorbent. Its dependence on the concentration of the adsorbate in the fluid is described by the adsorption isotherms. The specific surface area of an adsorbent is also critical in determining its capacity, which is why adsorbents preferably have a high porosity. A distinction is made between “external specific surface”, i.e., the geometric surface/mass ratio, and the “internal specific surface”, i.e., the pore surface/mass ratio. The prerequisite for the bonding availability of the internal surface is its steric accessibility for the adsorbate, i.e., its “exclusion limit” which is characterized in the case of chromatography, for example, by the molecular weight of globular proteins which just can no longer penetrate into the pores.
Adsorption ability may be inherent in a solid substance, e.g., in the case of activated carbon and hydroxyl apatite, or it may be achieved by “adsorptive modification” of a “base material,” i.e., a preferably adsorptively inert solid having a suitable morphology, consisting of covalent bonding of chemical units to superficial “anchor groups” of the base material, these chemical units being referred to as “ligands” which are preferably capable of selective bonding.
With the porous solids considered for use as base materials, a distinction is made between aerogels and xerogels, the former being characterized by a rigid structure which may also have continuous pores, and in most cases a high mechanical strength, which can be promoted in particular by a crystalline structure and whose pore sizes are usually directly accessible by measurement technology, including the BET method, while xerogels usually consist of crosslinked chains of a polymer that is originally soluble in the medium.
There is a large selection of particulate base materials with particle sizes between about 1 μm and several mm, including silica gels (silicon dioxide gels), porous glass, cellulose and organic polymers based on methacrylate and styrene as traditional aerogels, those which approach aerogels and in particular agarose gels as well as dextran gels, polyacrylamide gels and other synthetic polymer gels as traditional xerogels. In addition, there are composite gels in many combinations, where a xerogel is incorporated into the pores of an aerogel.
However, there are a number of disadvantages when such base materials are used to produce an adsorbent:
1. Loading of an adsorber with the corresponding adsorbent is complicated because irregularities, channeling and the like must be prevented. There are also unavoidable deleterious edge effects between the adsorbent and the adsorber housing.
2. There is an antagonism between the pressure drop and the transport kinetics such that the latter is facilitated by smaller particle sizes but the pressure drop is increased at the same time. Particles down to 1 μm in diameter, optionally even in a nonporous form, are therefore above all used for analytical separations in so-called HPLC (high performance liquid chromatography). For applications on an industrial scale, however, relatively large particles must be used in order to limit the pressure drop. The unfavorable transport kinetics in this case can be improved only slightly by using particulate perfusion matrices. In addition, a low pressure drop can be achieved only with approximately monodisperse spherical particles but these are much more expensive to produce in comparison with irregularly shaped particles.
Accordingly attempts have been made to avoid the disadvantages described above by using non-particulate adsorbents. The non-particulate adsorbents which have gained wide acceptance in practice are mainly in the form of compact bodies which are always perfusion matrices and flat configurations. A compact adsorbent is described in U.S. Pat. No. 6,048,457, the object of which is adsorbent bodies produced in situ in pipette tips, said adsorbent bodies consisting of particles of an adsorbent embedded in a porous polymer matrix. However, the production process does not offer good scale-up opportunities any better than those proposed by Svec (T. B. Tennikova et al., Journal of Chromatography, 555, (1991), pages 97 to 107) based on polymerization of ethylenically unsaturated monomers to form structures of a suitable shape and porosity. This latter process is limited by the impossibility of removing the reaction heat generated with larger units.
Flat adsorbents have a thickness of approximately 10 to 1,000 μm and can be processed to yield adsorbers of the desired dimensions. When they are perfusion matrices, they are called “adsorption membranes.” The traditional “filtration membranes” may be used as the base materials. These are flat aerogel sheets having average pore sizes from approximately 0.05 μm to 10 μm; they are referred to as asymmetrical when they have a pore size gradient over the thickness. Symmetrical however refers to membranes that do not have a pore size gradient over the thickness. The filtration membranes may come in different forms, e.g., flat membranes, hollow fiber membranes or tubular membranes. Filtration membranes, however, have the following disadvantages for adsorptive modification:
1. Most of the polymers suitable for producing them such as polysulfones, polyvinyl chloride (PVC), etc. do not have an adequate density of suitable anchor groups and they have a rather marked tendency to nonspecific adsorption.
2. In the pore size range which ensures a high hydraulic permeability, there is not a sufficient specific surface area to achieve high capacities.
3. The chemical conversion of sheet materials necessitates mechanically complex equipment for technical implementation and requires the use of large volumes of reaction media.
Adsorption membranes are available commercially under the name Acti-Disc (brand name of FMC Corporation, Philadelphia, and later Arbor Technologies, Inc., Ann Arbor, Mich.). These membranes are produced from the membranes described in U.S. Pat. No. 3,862,030 according to the company brochure B405 of Arbor Technologies, Inc. This membrane consists of a synthetic polymer having pores varying irregularly in the size range from 0.01 μm to 100 μm distributed irregularly over its thickness and containing particles. In the manner of a deep bed filter, it is impermeable for particles smaller than the largest pores, so it should even be suitable as a sterile filter. It follows from this that they become clogged sooner or later due to the particulate impurities that are always present in real media when these membranes are used in membrane chromatography, and this blockage cannot be reversed even by reversing the direction of flow (“backwashing”). Furthermore, the silica gel particles whose adsorptive properties have been modified according to the company brochure mentioned above and which are used in the membrane are not porous, which results in a low adsorption capacity. With regard to the production process, reference is made in the company brochure to U.S. Pat. No. 4,102,746, in which adsorptive modification of the particles is performed subsequently, i.e., when they are already in the membrane sheet. As with the product mentioned above, this has the abovementioned disadvantages of chemical reactions on the membrane sheet.
Membranes containing particles are also used in a variety of applications in the medical field. For example, U.S. Pat. No. 4,373,519 proposes the use of PTFE membranes containing dextran particles for wound closure but they are not suitable as adsorption membranes because of their lack of adsorption capacity. United States Patent Application Ser. No. A-2002/0,066,699 discloses a membrane consisting of a polymer matrix and adsorptive particles immobilized in the matrix. The membrane has a selectively permeable skin which is provided with openings at irregular intervals on both sides and is capable of remaining organic compounds from a biological fluid. The skin should prevent the penetration of its shaped constituents into the membrane matrix in the intended use of the membrane, namely static adsorption of chemicals from blood. The presence of a skin, in particular when it has large openings, is a disadvantage in adsorption membranes because in those areas where the skin occurs, the hydraulic permeability is reduced, whereas it is not reduced in the area of the openings. This results in irregular flow velocities through the membrane over the membrane area, which results in premature exhaustion of the adsorption capacity in regions of high hydraulic permeability and there is a flow-through of the adsorbate before exhausting the capacity of the entire membrane. U.S. Pat. No. 4,728,432 describes membranes containing adsorptive particles for use in an adsorber according to the principle of tangential separation of substances. In the preferred embodiments, the membrane contains a support with a network structure and has 40–45% free area which makes them unsuitable as an adsorption membrane for the same reasons as given above.